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ADVOCACY

JPPT | Position Statement

Medication Dosage in Overweight and Obese Children


Kelly L. Matson, PharmD; Evan R. Horton, PharmD; Amanda C. Capino, PharmD on behalf of the Advocacy Committee for
the Pediatric Pharmacy Advocacy Group

Approximately 31.8% of U.S. children ages 2 to 19 years are considered overweight or obese. This creates
significant challenges to dosing medications that are primarily weight based (mg/kg) and in predicting
pharmacokinetics parameters in pediatric patients. Obese individuals generally have a larger volume of
distribution for lipophilic medications. Conversely, the Vd of hydrophilic medications may be increased
or decreased due to increased lean body mass, blood volume, and decrease percentage of total body
water. They may also experience decreased hepatic clearance secondary to fatty infiltrates of the liver.
Hence, obesity may affect loading dose, dosage interval, plasma half-life, and time to reach steady-state
concentration for various medications. Weight-based dosing is also a cause for potential medication errors.
This position statement of the Pediatric Pharmacy Advocacy Group recommends that weight-based
dosing should be used in patients ages < 18 years who are < 40 kg; weight-based dosing should be used
in patients ≥ 40 kg, unless, unless the recommended adult dose for the specific indication is exceeded;
clinicians should use pharmacokinetic analysis for adjusting medications in overweight/obese children; and
research efforts continue to evaluate dosing of medications in obese/overweight children.
ABBREVIATIONS BMI, body mass index; PPAG, Pediatric Pharmacy Advocacy Group; TBW, total body weight;
Vd, volume of distribution
KEYWORDS drug dosage calculations; drug therapy; obese; overweight; pediatrics; pharmacokinetics;
therapeutic drug monitoring
J Pediatr Pharmacol Ther 2017;22(1):81–83

DOI: 10.583/1551-6776-22.1.81

Background The Issue


Following a dramatic increase during the past four Obese individuals possess a higher body proportion
decades, rates of overweight and obese American of fat and generally have a larger volume of distribution
children have leveled off since 2010.1 At present, ap- (Vd) for lipophilic medications due to distribution of
proximately 31.8% of U.S. children ages 2 to 19 years these drugs into adipose tissue. Conversely, the Vd of
are considered overweight or obese.1 Reports from the hydrophilic medications will be altered (i.e., increased
hospital setting have shown similar epidemiology for or decreased) in these individuals due to increased lean
pediatric patients.2-4 This epidemic creates significant body mass, blood volume, and decreased total body
challenges to medication dosage (primarily weight water percentage.8-10 Obesity may affect loading dose,
based [mg/kg]) and predicting pharmacokinetics (lack dosage interval, plasma half-life, and time to reach
of data) in pediatric patients. steady-state concentration for various medications.8,10,11
Pediatric patients are classified as overweight or Individuals with obesity also may have alterations
obese based on body mass index (BMI) percentile, or in metabolism and elimination. It is hypothesized that
their BMI in relation to other children of the same age obese patients have decreased hepatic clearance
and sex. Reference standards for BMI percentile have secondary to fatty infiltrates of the liver.11 Obesity may
been established for children ages 2 to 20 years by increase both phase I and II reactions; however, the
both the Centers for Disease Control and Prevention effect on renal clearance remains unknown.9,11 It has
(CDC) and the Institute of Medicine.5,6 Additionally, the been noted that kidney size increases with elevations
CDC has published sex-specific BMI-for-age growth in total body weight (TBW), resulting in increased
charts that can be used to determine a child’s BMI glomerular filtration rate, potentially requiring more
percentile. The CDC considers children between the frequent dosage of renally eliminated medications to
5th and 85th percentiles to be at a “healthy weight.” obtain therapeutic concentrations.8,9,11,12
Both the CDC and the American Academy of Pediatrics Patient Vd and clearance are vital for determining a
classify children with a BMI between the 85th and 95th medication dose. For obese children, TBW should be
percentiles as “overweight,” and those with a BMI > used to describe Vd and lean body weight to describe
95th percentile as “obese.”7 clearance.9,10,13 Additionally, drug solubility and the

www.jppt.org J Pediatr Pharmacol Ther 2017 Vol. 22 No. 1 81


Medication Dosage in Overweight and Obese Children Matson, KL et al

need for loading or maintenance dosage should be which poses a challenge for clinicians in optimizing
reviewed because these factors are important for de- medication therapy in obese/overweight children.
termining appropriate weight/size descriptors (i.e., TBW, Human intervention, applied judgment, dose-range
ideal body weight, adjusted body weight, body surface limits, and education should all be applied to limit the
area) to calculate the final dose.10,14,15 In obese children incidence of dosage errors in obese pediatric patients.
requiring loading doses, for hydrophilic medications,
use ideal body weight; for lipophilic medications, use Recommendations
TBW; for partially lipophilic medications, use adjusted
body weight.10,15 Lean body weight should be used for The Pediatric Pharmacy Advocacy Group (PPAG)
maintenance doses because it is most closely related continues to support the following discussion points
to lean body mass.9,10,15 Several studies have evaluated that may be useful in determining empiric medication
equations to estimate lean body mass in children and dosage in overweight/obese children based on weight-
adolescents;16-19 however, more research is needed to based dosage schemes:
support their use. As with chemotherapeutic agents, · Weight-based dosing should be used in patients
body surface area may also be considered as an ef- ages < 18 years who are < 40 kg;
fective body size descriptor for maintenance doses in · For children who are ≥ 40 kg, weight-based dos-
children ages 1 month to 14 years using the Mostellar ing should be used, unless the patient’s dose or
equation.10 dose per day exceeds the recommended adult
There are limited examples of altered pharmacokinet- dose for the specific indication; familiarity with
ic changes of medications in obese children within the adult dosage regimens is needed in order to
literature. Vancomycin has been the most extensively avoid exceeding the recommended maximum
studied with respect to dosage strategies in pediatric adult dose;
obesity. Data suggest dosage regimens be based on · Clinicians should consider pharmacokinetic analy-
TBW, although obese patients may require more vigi- sis for adjusting medications whenever possible
lant serum-level monitoring.20-23 Pediatric studies have in overweight/obese children to ensure the most
also recommended aminoglycoside dosage be based effective and safe regimen.
on either TBW or adjusted body weight.15,24,25 Kendrick The prevalence of overweight/obese children has
et al14 provide further dosage guidance in pediatric reached an epidemic level in the United States.
overweight and obese patients in an extensive review. Weight-based dosing is the most common scheme
in determining medication dosage in children. The
PPAG acknowledges that although studies continue
Medication Error
to examine dosing strategies in obese children, overall
The relative lack of standardized dosage regimens limited data are available in this population. The PPAG
for children, coupled with unknowns related to obe- continues to support research efforts to evaluate thera-
sity, is a cause for concern for potential medication peutic agents in obese/overweight children.
errors.26,27 Weight-based (mg/kg) and body surface
area–based (mg/m2) dosages are the most common ap- ARTICLE INFORMATION
proaches used in determing drug dosage.28-31 Specific
Affiliations University of Rhode Island College of Pharmacy,
determinates of pediatric to adult dosage conversions Kingston, RI (KM); UMass Memorial Children’s Medical Center,
do not exist, which may lead to the potential for over- Worcester, MA (KM); Pharmacy Practice, Massachusetts Col-
dose situations. For example, an 8-year-old weighing lege of Pharmacy and Health Sciences, Worcester, MA (EH);
90 kg who is prescribed 100 mg/kg/day of ceftriaxone Baystate Children’s Hospital, Springfield, MA (EH); Pharmacy
would receive a 9-g dose, which exceeds the maximum Practice, University of Mississippi School of Pharmacy, Jack-
recommended dose of 4 g/day.30 Conversely, early son, MS (AC)
conversion to adult dosage may lead to subtherapeutic
dosage. For example, an 8-year-old, 90-kg patient who Correspondence Pediatric Pharmacy Advocacy Group, jen-
is given the maximum adult recommended dosage of nifer.chow@ppag.org
1500 mg/day ( 16 mg/kg/day) of ciprofloxacin would
Disclosure The authors declare no conflicts or financial inter-
receive a dosage that is below the recommended 20 est in any product or service mentioned in the manuscript,
mg/kg/day in pediatric patients.30 including grants, equipment, medications, employment, gifts,
Incorrect dosage is the most commonly reported and honoraria.
error in children.32,33 To avoid errors, the American
Academy of Pediatrics requests each prescriber ensure Acknowledgment Authors on the first version were Peter
that the patient’s weight is appropriate for weight-based N. Johnson, PharmD; Jamie L. Miller, PharmD; Elizabeth A.
regimens, and that the dose does not exceed the rec- Boucher, PharmD; Lisa Lubsch, PharmD; Jennifer E. Girotto,
ommended adult dose.26 Unfortunately, data are lacking PharmD; Kimberly A. Pesaturo, PharmD; and Bernie R. Lee,
regarding maximum doses for specific medications, PharmD

82 J Pediatr Pharmacol Ther 2017 Vol. 22 No. 1 www.jppt.org


Matson, KL et al Medication Dosage in Overweight and Obese Children

Copyright Published by the Pediatric Pharmacy Advocacy 18. Ross EL, Jorgensen J, DeWitt PE, et al. Comparison of 3
Group. All rights reserved. For permissions, matthew.helms@ body size descriptors in critically ill obese children and
ppag.org. adolescents: implications for medication dosing. J Pediatr
Pharmacol Ther. 2014; 19(2):103-110.
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